Unraveling Complex Interactions Mechanisms Linking PTSD and Chronic Diseases

Post-traumatic stress disorder (PTSD) is a chronic and multifactorial psychiatric condition that is often underdiagnosed, particularly when associated with chronic diseases (CDs). These conditions arise from complex interactions among psychosocial, socioeconomic, epigenetic, immune, metabolic, and neurobiological factors. Current treatment options for PTSD and CDs, whether isolated or comorbid, remain suboptimal. Addressing the bidirectional relationship between PTSD and CDs is a pressing global public health challenge, necessitating a deeper understanding of the underlying molecular mechanisms. This review examines the interplay of stress-response and neurochemical factors in PTSD and CDs, highlighting how maladaptive stress responses to trauma can disrupt neurochemical pathways, contributing to the development of CDs, and vice versa. Despite this, a significant gap exists in the number of in vivo model studies that adequately mimic the comorbid symptoms of PTSD and CDs, hindering progress in elucidating shared cellular and molecular pathways. This limitation restricts therapeutic advancements. Therefore, a comprehensive understanding of the neurobiological dysfunctions in the brain and their crosstalk with the immune, cardiovascular, and endocrine systems is critical. Such insights will pave the way for individualized treatment strategies tailored to the unique profiles of patients with PTSD associated with CDs.